Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L).
Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L).
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DOI：
10.2337/dc12-2454
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发表时间：
2013-09
期刊：
影响因子：
16.2
通讯作者：
Rosenstock J
中科院分区：
文献类型：
--
作者：
Riddle MC;Aronson R;Home P;Marre M;Niemoeller E;Miossec P;Ping L;Ye J;Rosenstock J
目的：研究在已建立的基础胰岛素治疗基础上单独或与二甲双胍联合应用每日一次的高血糖素样多肽-1受体激动剂(GLP-1RA)来塞那肽治疗2型糖尿病合并糖化血红蛋白(HbA1c)升高的患者的有效性和安全性。我们进行了一项双盲、平行组、安慰剂对照试验。有基础胰岛素治疗但血糖控制不佳的患者(n=495)被随机分成两组，分别给予利塞奈德20μg或安慰剂治疗24周。除限制低血糖外，基础胰岛素剂量没有变化。糖化血红蛋白从基线水平下降是主要终点。糖尿病平均病程为12.5年，胰岛素使用时间为3.1年，胰岛素用量为55单位/天，基线糖化血红蛋白为8.4%。服用利昔那肽后，安慰剂校正后的HbA1c较基线的变化为-0.4%(95%CI-0.6to-0.2P=0.0002)，终点时的平均HbA1c为7.8%。受试者(28%)的糖化血红蛋白水平(7.0%)高于安慰剂组(12%；P<；0.0001)。标准早餐后，利昔那肽降低了血糖水平(安慰剂校正的降低值，-3.8mmo1/L；P<；0.0001)；七点血糖曲线显示一整天都有降低值。体重(安慰剂校正后，-1.30千克；P<；0.0001)和胰岛素用量(-3.7U/天；P=0.012)的减少幅度更大。利塞奈德的主要不良反应是胃肠道反应。症状低血糖：利塞那肽组为28%，安慰剂组为22%；328名受试者中有4人(1.2%)出现严重低血糖，而安慰剂组167人中为0。在基础胰岛素稳定但血糖控制不充分的2型糖尿病患者中，通过改善糖化血红蛋白和餐后高血糖而没有体重增加，利塞那肽可能会提供快速作用胰岛素或其他治疗方案的替代方案。
To examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA1c). We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA1c reduction from baseline was the primary end point. Mean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA1c from baseline was –0.4% (95% CI –0.6 to –0.2; P = 0.0002), and mean HbA1c at end point was 7.8%. HbA1c <7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P < 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, –3.8 mmol/L; P < 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, –1.3 kg; P < 0.0001) and insulin dosage (–3.7 units/day; P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo. By improving HbA1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.